Coccidiosis is an enteric disease of animals that afflicts domestic poultry and livestock worldwide. Businesses that rely on animal production often face significant costs because of coccidiosis, including financial losses due to the diseased livestock, as well as the expenses for the prophylactic treatments intended to reduce and/or prevent the disease. Such costs are especially relevant to the commercial and intensive animal industries, such as the poultry industry, where intensive housing of birds favors the spread of coccidiosis.
Members of the obligate intracellular sporozoa subclass, Coccidia, are the etiological cause of coccidiosis. One genus of Coccidia, Eimeria, has a significant impact on animal production. As is true for closely related genera Isospora, Cyclospora (Cystoisospora), and Cryptosporidium, Eimeria requires only a single host to complete its life cycle. Under natural conditions, this life cycle begins with the ingestion of sporulated oocysts from the environment.
Eimeria are single-celled parasites with a complex, monoxenous life cycle, that exhibit a high degree of both host-species and tissue specificity. Eimeria species include those that are found in chickens: E. tenella, E. acervulina, E. maxima, E. necatrix, E. mitis, E. praecox, E. mivati, E. hagani and E. brunetti; and those found in turkeys: E. meleagrimitis 1 (heretofore known simply as E. meleagrimitis), E. adenoeides, E. gallopavonis, E. dispersa, E. meleagridis, E. innocua, and E. subrotunda. 
In the field of avian coccidiosis, the amount of research on turkey coccidia is dwarfed by the amount performed on chickens. Indeed, worldwide whereas there are only two commercially available turkey coccidia vaccines (Coccivac-T®, first used in 1960's and Immucox®, first used in the 1980's), there are approximately a dozen chicken coccidia vaccines. Therefore, there remains a particularly strong need for additional and improved vaccines that can provide protection for turkeys against avian coccidiosis.
Numerous Eimeria species can infect a single host via the oral route, nasal route and/or by entry of the infectious particles into the lacrimal duct. Once ingested, the parasites penetrate the intestinal mucosal cells and undergo asexual and sexual stages of the life cycle. The resulting intestinal damage can ultimately lead to impaired growth (stunting), decreased feed utilization, loss of pigmentation, and increased mortality. In addition, the damage to the intestinal lining can predispose turkeys to other infectious agents.
The stages of the life cycle of Eimeria are essentially the same for all species of Eimeria, although each species has a preferred site in the intestine for development and the time required to complete the life cycle varies from species to species. Infection begins with ingestion by a host of sporulated Eimeria oocysts. The ingested oocysts then release sporocysts in the intestine of the host. The sporocysts release sporozoites that enter intestinal epithelial cells and then transform into trophozoites. The trophozoites, in turn, undergo a process known as merogony to form first generation schizonts. Due to the relatively large schizonts, such as in the case of E. necatrix or E. tenella, or the abundance of the schizonts, such as E. mivati, or the large gamonts as in the case of E. maxima, these are the stages that cause the principal pathogenic effect of the infection, i.e., the tissue damage to the host.
Mature first generation schizonts produce numerous merozoites which are released and invade new epithelial cells, then grow and form the next-generation of schizonts. These asexual phases continue for a variable number of generations prior to the beginning of the sexual phase. The sexual phase starts when the schizonts develop into gamonts; micro-gamonts and macrogamonts. The microgamonts subsequently develop into microgametes that fertilize the macrogamonts to produce unsporulated oocyst progeny. The unsporulated oocysts are then released into the intestinal lumen and excreted with the host feces. The completion of the endogenous life cycle, heralded by emergence of unsporulated oocysts in the host feces, is known as patency.
Sporulation of the oocysts occurs outside of the host, when the environmental conditions are favorable. The inevitable ingestion by a host of the sporulated oocysts begins the next cycle of infection. The time from host ingestion of the sporulated oocysts to emergence of the unsporulated oocysts in the feces is termed the prepatent period. The prepatent period differs among the various Eimeria species.
Poultry that are repeatedly exposed to Eimeria infections can acquire immunity to coccidiosis. In fact, depending on the immunogenicity of each Eimeria species, daily infection of turkeys with small numbers of sporulated oocysts can result in the birds acquiring full immunity after as little as two repeated infections. Consequently, current protocols employing live Eimeria vaccines are based on the principle of acquired immunity, i.e., repeated infections with a small number of infective oocysts.
Vaccination generally is performed in the hatchery on the day of the bird's hatch by administering the live Eimeria vaccine via a spray application (directly onto the birds). Ingestion of the sporulated oocysts during normal preening of the feathers then results in an oral inoculation of the vaccine. Alternatively or in conjunction, vaccines can be applied at a later date in the feed and/or drinking water. The infective oocysts complete their life cycle inside the intestinal tract of the bird, as described above, culminating with the release of a new generation of unsporulated oocysts in 5-11 days, depending on the species of the Eimeria. The unsporulated oocysts excreted with the feces then become infective, i.e., sporulate outside of the host, and re-infect the birds through host ingestion. Following two or three such cycles, the birds become immunized against the species of coccidia that they previously were exposed to. This immunity is characterized by protection against the disease or infectious agents as determined by: (i) a decrease and/or absence of parasites observed microscopically in the intestine, (ii) a reduction of the shedding of the oocysts, (iii) a reduction of the intestinal lesions, (iv) a reduction of the clinical disease, (v) a reduction or prevention of weight lost, and/or (vi) a reduction in the impairment of the efficiency of feed utilization. The acquired immunity wanes over time in the absence of subsequent exposure to infective oocysts.
Wild-type Eimeria are generally isolated from outbreaks of clinical disease in poultry flocks and may be propagated for use as pathogenic challenge strains. Typical non-attenuated vaccines are composed of infective oocysts from mildly to moderately pathogenic strains of the different Eimeria species that have been maintained by laboratory passage. These non-attenuated Eimeria are capable of causing coccidiosis when ingested in very high numbers. Vaccine makers and users have to be careful to ensure that the vaccination provides just enough infective oocysts to elicit immunity, but not disease in the naïve host. After the initial dose, the vaccination process relies solely on re-infection through the host's ingestion of sporulated oocysts from the litter.
The pathogenicity, pathology, and clinical signs for coccidiosis in the turkeys may be characteristic for each Eimeria species. The Eimeria generally isolated from commercial turkey farms are E. adenoeides, E. meleagrimitis 1, E. dispersa, and E. gallopavonis; the four coccidia that heretofore, were considered to be the only pathogenic turkey Eimeria species. E. adenoeides and E. gallopavonis parasitize primarily the ceca and rectum, and in most cases the lower portion of the ileum. In contrast, E. dispersa and E. meleagrimitis 1 parasitize the small intestine with the parasitism mainly residing in the upper and mid-small intestine. Patho-physiological changes such as increased water loss via the feces, increased mucus production and/or blood loss due vascular damage, result in impaired performance such as reduced growth rate, feed utilization and even mortality.
Recent outbreaks of coccidiosis in commercial turkey flocks demonstrate that existing control methods cannot alone impede Eimeria infections. Indeed, in view of the lack of good control from pharmaceuticals and or vaccines to counteract such Eimeria infections, there remains a longfelt need for new and/or improved vaccines that can better protect turkeys from this costly enteric disease.
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